Probably the most important task that I had when I ran a large clinic was to see as many patients as I could who had failed an IVF cycle. Invariably, the couples had one question. Should we try again? This is possibly the most complicated common question in the whole of reproductive medicine and it can be difficult to give good advice.
The first thing to remember is that most of the time, failure is simply a matter of statistical probability. IVF only has around a one in four chance of success. So much of the time, going through a repeated cycle is just about improving the odds a bit.
There may well be assessments the couple needs to make. A couple cannot always expect their doctor to advise them either way as, while there may be medical reasons for failure, a lot depends on how they felt about undergoing the treatment as well. Here is a list of some questions or points that may be helpful in trying to assess to this most difficult decision.
This is the first question couples should ask themselves. For some, going through IVF is a harrowing experience, one that they do not wish to repeat. For others, it is a great deal easier than they expected. If a couple found going through treatment depressing and difficult, then they should certainly think very seriously before trying again. I would strongly advise talking to a counsellor.
Nearly all good clinics offer an in-house counselling service which can really help anyone trying to arrive at decisions concerning repeated treatment. No counsellor will be able to tell you what to do, but he or she can help you to focus on the crucial aspects of how you feel, which will help you to make your own judgements.
This is a question that may not be possibly asked enough. IVF is expensive and the cost can increase with subsequent treatment cycles because as a woman gets older, she tends to need more drugs to stimulate the ovaries. It is quite common to need rapidly increasing amounts of gonadotrophin with successive treatment cycles, so the drug costs may spiral. I think there has to be serious assessment about whether it might be better to spend your money in other ways. This, I think, is particularly true for those who already have one child.
More and more of the larger clinics now have a large database which includes records of all of their treatment cycle attempts. Many of them use databases which give an analysis for at least five or six hundred cycles a year. Moreover, some of these clinics have been in existence for a long time and will have a broadened experience of various medical conditions that affect the chances of success or failure. They should be able to use these records to give couples an idea of their likely success or failure of another cycle based on the patients of a similar age with the same diagnosis. Obviously, the computer will not answer everything. For some people, a three per cent chance is worth taking. For others, a fifteen per cent chance is not worth consideration.
Some women clearly have a family history of an earlier than average menopause. It is worth finding out how old your mother was when you and your siblings were as well as when she stopped having periods. Women whose mothers tended to have an early menopause, may in turn themselves have an earlier than average menopause. Under these circumstances it may be worth trying another cycle treatment as soon as possible, then giving up, particularly if there is a poor response to superovulation. Such decisions will be helped by reassessing of FSH and AMH levels, the number of follicles seen in a typical menstrual cycle and the volume of the ovaries on ultrasound.
This is hugely important. A visit to the clinic for a troubleshooting session after failed IVF needs thorough an examination of your medical and laboratory records. There are a number of pointers that can help indicate whether further treatment may have a good prognosis.
Patients who require only a small amount of gonadotrophin are likely to have a much better chance of success should they repeat a treatment cycle. In general, this also tends to be true of patients with a tendency to hyperstimulation. Conversely, those women who need massive doses of drugs to induce ovulation are likely to have a poorer chance with successive attempts.
Women who yield a reasonably large number of eggs (more than seven or eight) have a statistically better chance of success in another treatment cycle than those that have yielded fewer than five. The number of eggs collected after stimulation is partly dependent on age. Clinics should be able to tell you the average numbers of eggs they expect from a given age. If you are much below this average, it is an indication that another treatment cycle is less likely to be successful. For example, a woman of 35 may produce an average of around ten eggs but a woman of 38 who is producing fewer than four eggs has a poor chance. If you have had several cycles, then adding up the total number of eggs you have produced may also be helpful; if the number of eggs is decreasing each time, this is further evidence of a reduced chance of success.
Many units take several blood samples to measure the oestrogen values during the IVF treatment cycle. These are a useful indication of how well the ovary has responded and what its chance is of responding in another cycle. Some units pay particular attention to the peak oestrogen value –the highest level achieved, usually just before the egg collection. Women with low levels, say below 2,500 pmols per litre, are likely to have a poorer chance of success in a further cycle. As successive treatment cycles are done, the ovaries tend to fail to respond. Poor response, in general, carries a poor. As with egg numbers, this too is to some extent age-related. Nevertheless, a woman of 42 with peak oestrogen levels of more than 5,000 pmols per litre is likely to have a much better chance of IVF success should she try again.
Women who produce poor quality eggs will tend to have a low fertilisation rate. The average, not using ICSI, should be around 60 per cent. Rates well below this level in the presence of normal sperm are likely to be producing eggs that may not give rise to a good embryo. Very poor fertilisation rates over several cycles indicate the poor prognosis. Some units try to get round this problem by forcing fertilisation with ICSI. I am not certain that ICSI is of much benefit in these circumstances – you cannot force a poor-quality egg to become a good embryo simply by injecting a sperm into it.
A previous treatment cycle may have generated a number of spare embryos, which may have been frozen. Some may have been grown for a while in culture. The observations made on the spare embryos’ culture can be valuable. If for example, a number of these embryos grew to the blastocyst stage, this is pretty good evidence that a couple is producing better than average embryos. A number of units are doing this research on spare embryos, and it is your prerogative to have access to these results.
Some units are now doing dynamic tests on embryos, which tell them more about the chromosomes within the embryos, and the chemicals the embryos are producing. These tests are likely to be increasingly valuable when used on spare embryos and, with further research, may also give clues as to the quality of the embryos that have been transferred.
If an IVF cycle has ended with a failed pregnancy even if it has been an ectopic, a miscarriage, or merely a biochemical pregnancy with a slightly raised level of HCG in the bloodstream, the prognosis is rather better for another attempt at treatment. Women who have had a child in the last four or five years, whether the pregnancy was conceived spontaneously, or by IVF have a better chance of success than women who have never conceived.
If the clinic and couple decide to have another attempt certain tests should be repeated before the next cycle –
Blood levels of FSH tend to rise as the ovaries fail so it should be measured between the day 5 and 9 of an unstimulated cycle. AMH is also useful, but unfortunately, the results of this test have still not been standardidsed so care is needed in interpretation. If the FSH level is much over 10 international units, then the chances of repeated IVF working are reduced as this indicate ovarian failure. If it is over 15 international units the chances of success are very poor and it is virtually never worth considering IVF if the level is over 20. Once the FSH level has been found to be raised – even if the level returns to normal – the prognosis is still poor.
Ultrasound can check for ovarian cysts, which may occur the following stimulation, and be used to measure the total volume of each ovary. Patients with very small ovaries, say less than 3 mm, are likely to have a poor response if ovulatory drugs are repeated.
Sometimes, regrettably, IVF units forget to assess the uterus. There is no question that this should be done before any fertility treatments. Nevertheless, if it has not been done, or not been done within the last four years, I recommend getting accurate information about the state of the uterine cavity and its surrounding muscle. Although units frequently offer a hysteroscopy, a better test is undoubtedly the hysterosalpingogram (HSG) X-ray. It is also cheaper. Frequently there are defects in the uterine cavity, which are correctable before considering another IVF attempt, or fibroids that should be removed.
Some men and women have unexpected chromosome problems that may give rise to their infertility, and which have not been diagnosed. It is may be worth getting blood tests from both partners to evaluate this if the cause of failure remains puzzling. These tests are not cheap, unfortunately. Ideally, a large number of white cells from the blood should be examined and not just the routine one or two. This is because sometimes people may be ‘mosaic’ (some cells in their body that have a normal chromosome complement and others which do not). Patients with a mosaic may have a slightly higher risk of producing abnormal embryos and a greater chance of infertility or miscarriage. If this is the problem, currently there is only a limited amount that can be done.
It is clear from various statistics that the chances of successful IVF are less good if there a woman has tubal disease. There is some evidence that patients with blocked fallopian tubes containing fluid (hydrosalpinx) do less well than patients who have normal tubes, or patients with damaged tubes which do not contain fluid. Some units claim to have had a better pregnancy rate if they prevent any infected fluid inside the fallopian tube from entering the uterus before repeating an IVF cycle. One approach is to remove the affected tube laparoscopically. Another strategy is to close the tube where it joins the uterus using the type of clips that are normally applied during sterilisation procedures. It is thought that this may decrease the chance of compromising the uterine environment. There is no clear statistically proved evidence that treatment of hydrosalpinges makes a difference and I am doubtful that it is necessary.
Despite countless breakthroughs in medical science, we still do not understand why some pregnancies will end in tragedy. For most of us, having a child of our own is the most fulfilling experience of our lives. All of us can imagine the desperation and sadness of parents who lose a baby, and the life-shattering impact that a disabled or seriously ill child has on a family.
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